The invention relates to a transdermal therapeutic system for delivering active agents to the human body through the skin.
Transdermal therapeutic systems have already been introduced in the market for the pharmaceutical treatment of a number of diseases and have proven themselves in practice.
Moreover, a number of different possible system designs are known in the art (see for example Y. W. Chien in: A. F. Kydonieus and B. Berner (eds.) "Transdermal Delivery of Drugs", p. 81-100).
There are some fundamental similarities, however, independent of the variety of possible system designs between the systems known in the art these similarities are:
1. For protection against unwanted delivery of the active agent or skin moisture by the transdermal therapeutic system and also for protection against adhesion to textiles, an essentially impermeable, non-sticking backing layer (1) is used.
2. Since transdermal therapeutic systems have to stick on the skin, the layer facing the skin, and occasionally only a part of the area facing the skin is made from a pressure-sensitive adhesive.
3. Because of these self-adhesive qualities, a removable protective layer (3) made from a non-adhesive material, if necessary, is added to the transdermal therapeutic system.
The backing layer consists of the usual pharmaceutical materials, such as plastic webs, papers, nonwovens or textiles. Frequently, thermoplastic plastics are used because of their easy processability, such as extruding or casting, stretching along the length or cross in the case of films or also in form of fibers in their use as non-woven-like or textile applications.
Specifically suited plastics are exemplified by polyethylene terephthalate (PETP) and other polyesters, polyethylene (HDPE or LDPE), polyvinyl chloride (PVC, optional softenized), ethylene-vinyl acetate-copolymers (EVA) and polypropylene (PP). In order to combine advantageous features, laminates can be used (for example EVA or PE (outer surface) and PETP). The surface (4) can be (PE or EVA) equipped with skin-like soft "touch" and on the other side, a PETP layer (5) may act as a diffusion barrier against the active substance of the transdermal therapeutic system.
Similarly, as in the case of conventional pharmaceutical application forms, the marketing companies, the regulatory agencies or consumer organizations wish or even require the clear identification of the systems. In this way, a positive identification of the product is necessary when the package leaflet and other accompanying information is not available. Form, size and appearance alone cannot ensure positive identification.
It has become therefore conventional in the art to print such systems with a suitable printing ink on the outside of the backing layer. This possibility, described in EP 0 114 125, allows easy identification and makes colored noticeable features possible.
Furthermore, it is known by those skilled in the plastics art that thermoplastic plastics are deformable under heat and a change of shape may be used to emboss patterns or information on everyday commodities, and also on plastic laminates (see e.g., U.S. Pat. No. 4,359,442).
For the labeling of articles, especially in the packing of pharmaceutical products, however, only transfer printing is usually used in which a pigmented plastic laminate is pressed for a short period of time against the matter to be printed. This allows the ink pigment to be applied onto the substrate.
Also embossing is known as a procedure to label transdermal therapeutic systems (DE-Gbm 94 9 784). Here, a sheet-like means of labeling with embossments or prints are applied on the drug-containing part of patches containing pharmaceutical agents.
This state of the art nevertheless has a number of disadvantages: with the use of (only toxicologically acceptable) printing inks, to work with solvent-containing carrier fluids for pigments and varnishes at the place of the manufacture of pharmaceutical products is problematic because of possible contamination with foreign materials.
A number of varnishes do not or only insufficiently stick on the backing material; this way only printable materials are suitable.
The printing ink on the transdermal therapeutic systems may soften during storage and the imprint becomes unreadable upon the influence of volatile agents in the transdermal therapeutic system.
Furthermore, a color print code on the transdermal therapeutic system is disturbing cosmetically for the consumer.
If, as in DE-Gbm 94 9 784, embossing is chosen for application of the coding, at application of ordinary techniques accessible for those skilled in the art, the drug-containing part has to be exposed to an undue and high pressure, noxious for the pharmaceutical form of application.
Compression of the matrix in this way easily leads to local changes of the function of the patch, particularly the release in vitro. An embossment performed prior to application of a sheet-like carrier of label requires a second pressure sensitive adhesive intermediate layer which usually leads to a bubble-containing unattractive appearance.
The embossment mentioned in DE-Gbm 94 09 784 is not described technically more precisely in the detail there. The use of a backing made of a uniform polymer material, which is the predominant use, an embossment, in any way performed, with or without the action of heat, causes the production of "thin areas". This may destroy the barrier property of the backing for the active agent and obviously, for this reason, embossing is not done in practice.